1. Field of the Invention
The present invention pertains generally to spectroscopic measurement apparatus, and more particularly to spectroscopic measurements based on light-molecule interaction in response to a resonant rate optical pulse train.
2. Description of Related Art
Performing biological analysis typically requires invasive procedures, such as in discriminating between healthy tissue and cancerous tissue. It is, therefore, an object of some investigation to provide an ability to study a biological samples acquired in a non-pharmaceutical and low-invasive, such as in response to vibrational spectrum data derived from a molecule. A vibrational spectrum in the fingerprint region has been used in analysis of a biological sample, while using a vibrational spectrum in a far infrared region lower than or equal to several terahertz in analysis of a biological sample is more recently under study. A terahertz vibrational spectrum derived from a biological macromolecule, which reflects a vibrational form in which a large number of atoms undergo collective displacement (collective mode) and a hydration structure, can be sensitive to global motion specific to a molecular structure and structural change in function expression. A terahertz vibrational spectrum is therefore expected to provide information complementary to vibrational spectroscopic information in the fingerprint region in analysis of a biological sample.
Terahertz absorption spectroscopy and spontaneous Raman scattering spectroscopy have been known as technologies for observing a terahertz vibrational spectrum derived from a biological sample. Since terahertz absorption spectroscopy involves irradiating a biological sample with far infrared light and measuring an absorption spectrum, the fact that water and biological macromolecules absorb and attenuate the diagnostic light impedes the spectrum measurement. In Raman scattering, narrow-band near infrared or visible light is typically used to excite a biological sample and non-elastically scattered light from the sample is measured. When a spectrum in a low-energy region lower than or equal to several terahertz is observed in the spontaneous Raman scattering spectroscopy, background light including elastically scattered light impedes the measurement.
Another terahertz vibrational spectrum observation approach other than the methods described above is coherent vibrational spectroscopy performed in a temporal region. Impulsive stimulated Raman scattering (ISRS) spectroscopy involves irradiating a sample with femtosecond pulse light to coherently excite a plurality of molecular vibrations in a stimulated Raman scattering process. The temporal profile representing the change in probe light due to the coherently excited molecular vibrations is Fourier transformed so that a frequency spectrum is acquired. In ISRS, since near infrared light, which is not greatly absorbed by a biological sample, can be used and a directional signal light is detected, the influence of background light resulting from a linear process can be minimized. The method described above has been applied to limited applications, such as studies on physical properties of solid and liquid molecules.
However, when terahertz spectroscopic information is used to analyze a biological sample, any of the detection methods described above, which allows change in the hydration state of the sample or any other macroscopic state change to be observed, hardly allows any information on a molecule or a group of molecules in a protein or any other biological substance to be extracted. The reason for this is that a terahertz vibrational spectrum derived from a biological molecule under physiological conditions has a shape that lacks any band structure because of mode denseness and damping, and that bands derived from a plurality of molecules in a biological sample are superimposed, resulting in a dull spectrum. Therefore, to acquire information on a molecule in a biological sample, it is necessary to use an approach for extracting mode information that characterizes the structure of the molecule from a structureless spectrum.
Further, as an application of ISRS to a field other than spectroscopic analysis, using the method described above to control a vibrational quantum state of a molecule is under study. In a biological application, when a biological macromolecule in a biological sample is excited in an ISRS process to vibrate in a collective mode, it is conceivable that higher-order structural change of the molecule may be induced and a physiological function in the organism may change. It has been pointed out that the viruses are possibly inactivated because the collective mode of a coat protein is excited in a stimulated Raman scattering process excited by the femtosecond pulse light and the structure of the protein is changed. It will be appreciated therefore, that excitation of a biological macromolecule in the collective mode affects an organism.
Accordingly, a need exists for a system and method of obtaining detailed molecular information in a non-invasive manner.